A multiscale analysis in CD38 −/− mice unveils major prefrontal cortex dysfunctions

Abstract : Autism spectrum disorder (ASD) is characterized by early onset of behavioral and cognitive alterations. Low plasma levels of oxytocin (OT) have also been found in ASD patients; recently, a critical role for the enzyme CD38 in the regulation of OT release was demonstrated. CD38 is important in regulating several Ca 2+-dependent pathways, but beyond its role in regulating OT secretion, it is not known whether a deficit in CD38 expression leads to functional modifications of the prefrontal cortex (PFC), a structure involved in social behavior. Here, we report that CD38 2/2 male mice show an abnormal cortex development, an excitation-inhibition balance shifted toward a higher excitation, and impaired synaptic plasticity in the PFC such as those observed in various mouse models of ASD. We also show that a lack of CD38 alters social behavior and emotional responses. Finally, examining neu-romodulators known to control behavioral flexibility, we found elevated monoamine levels in the PFC of CD38 2/2 adult mice. Overall, our study unveiled major changes in PFC physiologic mechanisms and provides new evidence that the CD38 2/2 mouse could be a relevant model to study pathophysiological brain mechanisms of mental disorders such as ASD.-Martucci, L. A multiscale analysis in CD38-/-mice unveils major prefrontal cortex dysfunctions.
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Soumis le : jeudi 22 août 2019 - 14:23:17
Dernière modification le : jeudi 5 septembre 2019 - 16:47:09

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Lora Martucci, Muriel Amar, Rémi Chaussenot, Gabriel Benet, Oscar Bauer, et al.. A multiscale analysis in CD38 −/− mice unveils major prefrontal cortex dysfunctions. FASEB Journal, Federation of American Society of Experimental Biology, 2019, 33 (5), pp.5823-5835. ⟨10.1096/fj.201800489R⟩. ⟨hal-02269129⟩

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